When the coronavirus wields its spike protein in an attempt to break into your cells, not all targets are created equally. Researchers at Cambridge University wanted to know which of our cells and organs are most vulnerable to infection so they looked for the ones that make it easiest for the virus to latch on and get replicating. So what parts of your body are the virus’ favorite routes of infection and why? And how does knowing the virus’ entryway help us figure out better ways of keeping it out?
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Betrayed by your nose
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A new study published in Nature and led by a team at Cambridge University’s Wellcome Sanger Institute found that nasal epithelial cells—the cells on the inner lining of your nose—are likely the most effective route for you to become infected.
In order to find which cells might be the gateways for the virus, Cambridge researchers turned to the Human Cell Atlas. The atlas, launched in 2016, acts as a kind of map for the hundreds of different kinds of cells in your body, their characteristics, the genes they contain, and their relationship to other cells.
The coronavirus works by attaching its spike protein to a particular receptor on the outside of human cells referred to as ACE2 and a protein in cell membranes named TMPRSS2 which primes those receptors for the virus to enter. The cells with the highest levels of ACE2 and TMPRSS2 turned out to be in the nose — goblet cells that make mucus and ciliated cells, tiny cells that look like miniature wheat fields which clean stray bits of snot and foreign organisms out of your airways.
While the highest levels of ACE2 and TMPRSS2 were found in cells in the nose, the Cambridge team also found high levels in cells associated with other organs. Cells in the human cornea and intestines also had plenty of the coronavirus-friendly proteins, suggesting that SARS-CoV-2 might have other pathways into your body either through your eyes or in your poop.
That lines up with previous research into possible viral infection routes.
Scientists have already found that other coronaviruses can infect people through contact with infected droplets. At the outset of the pandemic, a pneumonia specialist in China became infected after inspecting a hospital while wearing an N95 mask and no eye protection and developed conjunctivitis shortly before becoming symptomatic.
Researchers have also found the virus present in our poop leading scientists and engineers in Europe and the U.S. have started testing sewage systems to detect outbreaks in municipal areas.
Playing both sides
Blame your nasal epithelial cells for being prey to the coronavirus if you want but the Nature study suggests that you might need help from those same cells later on. Researchers found that those same cells don’t just produce the receptors but are “associated with immune functions including innate and antiviral immune functions.” In that sense, your nasal epithelial cells appear to play a dual role in both making you vulnerable to the virus while also playing a key role in fighting it off once you’re infected.
“Given their environmental exposure and the high expression of entry genes for multiple respiratory viruses, it is plausible that the nasal epithelial cells were conditioned and primed to express these immune-associated genes to prevent viral susceptibility for these viruses,” Dr. Waradon Sungnak, the lead author of the study, wrote in an email to The Daily Beast.
Nose to the grindstone
The research does more than just satisfy our curiosity about how the virus gets inside. It also could be helpful in developing tools to keep it out.
“This points towards which cells any drugs would need to act on, or which cells to ‘protect’ from the virus to reduce transmission – eg nose and eyes. Given the importance of nasal epithelium as potential targets and reservoirs of the virus, it is possible that drugs administered nasally could limit the spread. It also suggests that vaccines could be nasally administered, avoiding use of needles and increasing the speed of vaccination,” Sungnak told The Daily Beast.
“When cells are damaged or fighting an infection, various immune-associated genes are activated. The study showed that ACE2 receptor production in these nose cells is probably switched on at the same time as these other immune genes. It is possible that this mechanism could provide drug targets to develop new treatments,” Sungnak added.
There’s some evidence to suggest that nasally administered vaccines might work if scientists can find a successful candidate. After a 2003 pandemic of SARS, a virus from the same family as SARS-CoV-2, researchers found that a nasal spray vaccine for the SARS virus administered to monkeys worked well.
